[Fats and oils (including omega3, omega6)]. / Fette und Ole (unter anderem Omega 3, Omega 6).

Saturated fatty acids contribute essentially to atherogenesis, especially to coronary artery disease. In contrast, the protective effect of monounsaturated fatty acids such as oleic acid, contained in olive oil and as a constituent of a Mediterranean diet is very well shown epidemiologically. There is a modest beneficial effect on the clinical manifestation of coronary heart disease when saturated fatty acids of animal provenience are partially replaced by omega 6 fatty acids (linoleic acid). However, studies with the addition of omega-3-fatty acids in the diet (fish oil rich in eicosapentaenoic and docosaexaenoic acid and rape seed oil rich in alpha linolenic acid) demonstrate a significant decrease of sudden cardiac death and non fatal myocardial infarction. Long-chain omega-3-fatty acids have a direct antiarrhythmic effect on myocytes. The reduction of non-fatal myocardial infarctions during consumption of diets rich in long chain omega-3-fatty acids could at least in part be attributed to inhibitory effects on platelet aggregation and thus on thrombus formation and to a stabilization of atherosclerotic plaques.

Short-term effects of atorvastatin on C-reactive protein.

AIM: To study the short-term effect of atorvastatin on C-reactive protein (CRP) in patients with or at risk for coronary heart disease. METHODS AND RESULTS: One hundred and fifty-five randomly selected patients from the SWiss Intervention Trial for lowering CHolesterol (SWITCH) were assessed for high sensitivity CRP, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides at baseline, and after 1 and 3 months of treatment with atorvastatin at various doses to reach pre-defined lipid target values. The median decrease of cholesterol was 28% after 1 month and 35% after 3 months. LDL-cholesterol was decreased by 37% and 45%, HDL-cholesterol was increased by 7% and 8%, respectively. Patients with a low CRP baseline concentration (lowest quartile <1.34 mg. l(-1)) displayed no significant change, whereas patients in the other quartiles showed a significant decrease, of 22% to 40% (P -value <0.05 to <0.001) at 1 month and of 32% to 36% after 3 months compared to baseline. The decrease in CRP lowering was thus fully established by 1 month and this response was independent of lipid and lipoprotein changes as well as atorvastatin doses. CONCLUSION: Atorvastatin significantly decreases CRP concentrations after 4 weeks of therapy. These results may be important with respect to the early benefit of statin therapy.

[Epidural hematoma in a child with hemophilia: diagnostic difficulties]. / Hématome épidural chez l'enfant hémophile: difficultés diagnostiques.

UNLABELLED: Spinal epidural hematoma is an uncommon complication in hemophilia. CASE REPORTS: The cases of an extensive epidural hematoma in two boys with severe hemophilia are reported. CONCLUSION: Acute onset of severe neck pain or backache leads to the diagnosis of epidural hematoma in children with hemophilia, even in the absence of neurologic symptoms. Early diagnosis is important and relies on magnetic resonance imaging. Replacement therapy is mandatory and must be prescribed before neuroradiologic imaging. Generally, children have a good neurologic outcome.

[Evaluating the efficacy and tolerance of atorvastatin in hyperlipidemia in general practice (SWITCH Study)]. / Prüfung der Wirksamkeit und Verträglichkeit von Atorvastatin bei Hyperlipidämie unter Praxisbedingungen (SWITCH-Studie).

Elevated levels of serum lipids and lipoproteins are known to play a major role in the development of atherosclerosis and subsequent coronary heart disease (CHD). In controlled clinical studies, atorvastatin (Sortis), a new 3-hydroxy-3-methyl-glutaryl-coenzyme-A (HMG-CoA)-reductase inhibitor, proved to be a very effective and safe lipid-lowering agent. The aim of this open-label, multicentre study (without a control group) was to confirm the efficacy and safety of atorvastatin in a private practice group, including 181 Swiss cardiologists, internists, and general practitioners. A total of 877 hyperlipidaemic patients requiring treatment participated in this study. To evaluate the effectiveness of the treatment with atorvastatin over a period of 12 weeks, total plasma cholesterol (TC), HDL cholesterol, LDL cholesterol and triglycerides (TG) were determined every 4 weeks. The initial atorvastatin dose was 10 mg in 78% of patients and 20 mg in 22%. The dose was doubled every 4 weeks until the target values of TC < or = 5.2 mmol/l and TC/HDL < or = 5 were reached. After 12 weeks of treatment with atorvastatin the mean reduction in TC, TC/HDL, LDL and TG compared to baseline levels was 33, 37, 42, and 25% respectively. At the same time the HDL concentration was increased by 9%. These results were evidenced in patients with existing coronary heart disease, in high risk patients without manifest coronary heart disease and in patients with significantly elevated lipid levels (TC > 7.8 mmol/l, TC/HDL > 6.5). After treatment with atorvastatin for 12 weeks, 59% of patients had reached the therapeutic target of TC < or = 5.2 mmol/l. The target of TC/HDL < or = 5 was reached by 79%. Atorvastatin was almost without exception well tolerated, the most frequently reported side effects being nausea, myalgia, and headache. In this open-label multicentre study atorvastatin was found to be effective and well tolerated. The observed reduction in the lipid and lipoprotein concentration is in accordance with the results of published controlled studies. The lipid and lipoprotein concentrations were decreased significantly in patients with slight to moderate elevation of lipid levels as well as in those with significantly raised values.

Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group.

OBJECTIVE: To determine the effect of orlistat, a new lipase inhibitor, on long-term weight loss, to determine the extent to which orlistat treatment minimizes weight regain in a second year of treatment, and to assess the effects of orlistat on obesity-related risk factors. RESEARCH METHODS AND PROCEDURES: This was a 2-year, multicenter, randomized, double-blind, placebo-controlled study. Obese patients (body mass index 28 to 43 kg/m2) were randomized to placebo or orlistat (60 or 120 mg) three times a day, combined with a hypocaloric diet during the first year and a weight maintenance diet in the second year of treatment to prevent weight regain. Changes in body weight, lipid profile, glycemic control, blood pressure, quality of life, safety, and tolerability were measured. RESULTS: Orlistat-treated patients lost significantly more weight (p<0.001) than placebo-treated patients after Year 1 (6.6%, 8.6%, and 9.7% for the placebo, and orlistat 60 mg and 120 mg groups, respectively). During the second year, orlistat therapy produced less weight regain than placebo (p = 0.005 for orlistat 60 mg; p<0.001 for orlistat 120 mg). Several obesity-related risk factors improved significantly more with orlistat treatment than with placebo. Orlistat was generally well tolerated and only 6% of orlistat-treated patients withdrew because of adverse events. Orlistat leads to predictable gastrointestinal effects related to its mode of action, which were generally mild, transient, and self-limiting and usually occurred early during treatment. DISCUSSION: Orlistat administered for 2 years promotes weight loss and minimizes weight regain. Additionally, orlistat therapy improves lipid profile, blood pressure, and quality of life.

Lipid-free apolipoprotein (apo) A-I is converted into alpha-migrating high density lipoproteins by lipoprotein-depleted plasma of normolipidemic donors and apo A-I-deficient patients but not of Tangier disease patients.

Plasma of patients with Tangier disease (TD) is devoid of alpha-LpA-I (apolipoprotein A-I-containing lipoprotein), which in normolipidemic plasma constitutes the majority of high density lipoprotein (HDL). The residual amounts of apolipoprotein A-I (apo A-I) in TD plasma have electrophoretic prebeta1-LpA-I mobility. We have previously demonstrated that TD plasma does not convert prebeta1-LpA-I into alpha-LpA-I. In this study we found that plasmas of normolipidemic controls, apo A-I-deficient patients and patients with fish-eye disease, but not plasmas of six TD patients, convert biotinylated lipid-free apo A-I into alpha-LpA-I. Supplementation of plasma with free oleic acid or fatty acid free albumin neither inhibited conversion activity in normal plasmas nor reconstituted it in TD plasma. In normal plasma the conversion activity was assessed in HDL and in the lipoprotein-free fraction. The latter fraction, however, generated larger particles only in the presence of exogenous phospholipid vesicles. To obtain particles with alpha-mobility, these vesicles had to contain phosphatidylinositol and/or cholesterol. Lipoprotein-depleted TD plasma did not convert lipid-free apo A-I into alpha-LpA-I even in the presence of exogenous vesicles with phospholipids or cholesterol. Taken together we conclude that disturbed transfer of glycerophospholipds onto apo A-I or prebeta1-LpA-I prevents maturation of HDL and thereby possibly causes deficiency of HDL cholesterol in patients with TD. Moreover, the lack of alpha-LpA-I in TD plasma together with its failure to convert exogenous apo A-I into an alpha-migrating particle provide specific tests for the diagnosis of TD.

Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I.

Plasmas of patients with Tangier disease (TD) lack lipid-rich alpha-HDL which, in normal plasma, constitutes the majority of high density lipoprotein (HDL). Residual amounts of apolipoprotein (apo)A-I in TD plasma occur as lipid-poor or even lipid-free prebeta-HDL. By contrast to normal plasma, TD plasma does not convert prebeta-HDL into alpha-HDL. Moreover, fibroblasts of TD patients were found to be defective in secreting cholesterol or phospholipids in the presence of lipid-free apoA-I. We have therefore hypothesized that both defective conversion of prebeta-HDL into alpha-HDL and defective lipid efflux from TD cells onto lipid-free apoA-I result from a disturbance in phospholipid transfer occurring in both cellular and extracellular compartments. To test this hypothesis we established an assay that measures the activity of plasma, cells, and cell culture media to transfer radiolabeled phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) from vesicles onto apoA-I, apoA-II, albumin, or reconstituted HDL. Plasmas, HDL, and lipoprotein-depleted plasma of normolipidemic probands as well as cell homogenates and culture media of normal fibroblasts were active at 37 degrees C but not at 4 degrees C in transferring radiolabeled PC, PI, and PE dose- and time-dependently onto either lipid-free apoA-I or reconstituted HDL. Transfer of glycerophospholipids onto apoA-II was much lower than onto apoA-I; transfer onto albumin was close to background. Compared to ten normolipidemic plasmas and four apoA-I-deficient plasmas, plasmas of six TD patients were significantly reduced by 40-50% in their glycerophospholipid transfer activities. Compared to eight normal fibroblast cell lines, homogenates and culture media of four TD fibroblast cell lines were reduced by 40-50% and 30-35%, respectively, in their activity to transfer PC, PI, or PE onto apoA-I. Our data suggest that in TD the same mechanism underlies both defective conversion of prebeta-HDL into alpha-HDL and impaired efflux of cellular lipids, namely a defective phospholipid transfer.

[Cholesterol crystal embolisms: an exciting search for "pearls"]. / Cholesterin-Kristall-Embolien: Eine spannende "Perlensuche".

This article is meant to increase the interest in an often forgotten clinical entity. Cholesterol emboli are in the majority of cases only diagnosed at post-mortem examination. Even though the triad livedo reticularis, renal failure and eosinophilia constitutes its most prominent feature, the variable clinical manifestations of this disorder with multiorgan involvement ("pseudovasculitis") make the search for cholesterol crystals particularly exciting. The discovery of 10 cases of cholesterol emboli over 2 years in a regional hospital's internal medicine department demonstrates that this occurrence is not rarely and that its accurate identification can be particularly relevant. It is important to recognize this disease since it is often iatrogenic, affects elderly people with atherosclerosis of the large vessels and causes high morbidity and mortality.

[A case of postprandial hypotension in an elderly subject]. / Un cas d'hypotension postprandiale chez un sujet âgé.

This is a case report of a 74-year old woman who from March 1994 to April 1995 was admitted to our hospital because of three episodes of syncope. Each general physical examination was normal except for a grade 2/6 systolic murmur. No abnormalities were disclosed after several resting electrocardiograms and Holter monitoring. The Schellong and the tilt tests were normal. During the last admission the patient had a syncope 30 minutes after a meal. Blood pressure reduction was documented and postprandial hypotension was diagnosed. Postprandial decreases in systolic blood pressure in the elderly may predispose the subject to symptomatic hypotension and to falls, dizziness, weakness, angina pectoris, stroke and syncope. The mechanism of postprandial hypotension is not fully understood. It is defined as a decrease in postprandial systolic blood pressure of 20 mmHg or more. Because postprandial hypotension is a common problem in older, frail, institutionalized patients, all physicians caring for elderly patients should be aware of the hypotensive effects of food intake and should consider postprandial hypotension in the evaluation of falls, syncope and other ischemic cerebral symptoms.

[Acute basal ganglia necrosis with favorable course during Mycoplasma encepahlitis]. / Nécrose aiguë des noyaux gris d'évolution favorable lors d'une encéphalite à mycoplasme.

BACKGROUND: Acute bilateral striatal necrosis complicating the course of a post-infectious encephalitis is rare. CASE REPORT: A previously healthy 5-year-old boy presented with an atypical pneumonia; he rapidly developed, encephalitis revealed by a generalized status epilepticus. After transient improvement, he became confused and mutic, with dystonic postures of his limbs. Painful stimulation resulted in prolonged facial grimacing and doleful cry. CT scan and MRI showed abnormal signals in the whole basal ganglia, typical of bilateral striatal necrosis. Serologic tests for Mycoplasma pneumoniae were positive. The child recovered almost completely. CONCLUSION: A parainfectious process is probably responsible for the transient bilateral striatal necrosis seen in this patient who had Mycoplasma pneumoniae infection several days before the onset of neurologic symptoms. MRI seemed more reliable than CT-scan for the diagnosis of this condition.

Separation between HIV-positive women and their children: the French prospective study, 1986 through 1993.

OBJECTIVES: We studied the risk and circumstances of separation (due to either maternal death or drug use) between women infected by human immunodeficiency virus (HIV) type 1 and their children. METHODS: This analysis was based on the French Prospective Study of Infants Born to HIV-seropositive Women (1986 through 1993). Data recorded at each follow-up visit included the mother's effective presence with the child and the child's care after separation. RESULTS: A child's cumulative risk of long-term or permanent separation from his or her mother was 37% at 60 months. Maternal drug use was associated with an added risk during the child's first years (adjusted relative risk [RR]=3.4, 95% confidence interval [CI]=2.3, 5.0). The risk among drug users was even higher when the mother used injection drugs during pregnancy (adjusted RR=2.9, 95% CI=1.9, 4.3). Risk of early separation related to drug use tended to diminish since survey initiation. After separation, 57% of the children were placed through child welfare services and 43% were cared for by relatives. CONCLUSIONS: In the French Prospective Study, 2% to 3% of HIV-infected children were separated each year from their mothers as a result of the mothers death from acquired immunodeficiency syndrome (AIDS). Separations related to drug use have decreased over the years, and the family is becoming the most frequent carer after separation.

Evaluation of efficacy and safety of erdosteine in patients affected by chronic bronchitis during an infective exacerbation phase and receiving amoxycillin as basic treatment (ECOBES, European Chronic Obstructive Bronchitis Erdosteine Study).

An international multicentric study was conducted with the aim of demonstrating that erdosteine improves the efficacy of amoxycillin in the treatment of infective exacerbation of chronic bronchitis mainly on the clinical symptomatology (primary objective), on spirometric tests and body temperature, without negatively influencing the tolerance (secondary objectives). The study was conducted as a prospective evaluation, with 2 comparative groups treated with erdosteine (300 mg x 2/day) or placebo in association with amoxycillin (1500 mg/day) for a maximum of 10 days. The design of the trial was double-blind and parallel group with 2 subgroups. The treatments have been assigned randomly to a population of chronic bronchitic patients in exacerbation phase of n = 237 subjects. The study was conducted according to the principles of the Declaration of Helsinki and its amendments (Hong Kong, September 1989). The primary end-point used to determine effectiveness in this study was the global clinical assessment (GCA) which was choosen as a general indication of activity with objective/subjective evaluation of the clinical picture. Secondary endpoints of efficacy are sputum parameters, functional signs of chronic obstructive bronchitis, spirometric tests and overall judgement of efficacy. Safety was evaluated with adverse drug reactions reporting, arterial blood pressure, heart rate and laboratory tests monitoring. The obtained values have been analyzed with two-way and factorial ANOVA, Least Squares Catmod-SAS, Wilcoxon and Chi-square tests. The number of patients included in the effectiveness analysis is of n = 226 subjects, due to the fact that 11 patients were lost due to different reasons. In term of results as far as the primary objective of the study was concerned, erdosteine resulted more active than placebo. The analysis evidenced a very significant difference for treatment, time and interaction time x treatment. No difference on the contrary was observed for center and the interaction center x treatment. Sputum volume, body temperature and spirometric parameters were not significantly influenced by both treatments. Viscosity, appearance as well as functional signs evidenced a modification over time in favour of erdosteine. As safety is concerned the majority of adverse events, both in the erdosteine and in the placebo group, were related to the gastrointestinal area. For erdosteine, of 9/17 side-effects, 3 were epigastralgias, 3 nauseas, 1 diarrhoea, 1 taste loss, 1 hemorrhoids. For placebo of 13/17 related events 3 were epigastralgias, 4 nauseas, 4 diarrhoeas, 1 pyrosis, 1 dry mouth. In terms of severity they have been all defined as mild or moderate degree. Also from a qualitative perspective it is clear that there are no relevant differences between the 2 treatments under evaluation, concerning safety. In conclusion of particular interest is the datum arising from the efficacy/safety evaluation, which indicates that the clinical picture is modified earlier and at deeper degree by the synergistic activity of erdosteine and of the antibiotic without the risk of an augmentation of side-effects incidence.

Reverse cholesterol transport in plasma of patients with different forms of familial HDL deficiency.

HDLs encompass structurally heterogenous lipoproteins that fulfill specific functions in reverse cholesterol transport. Two-dimensional nondenaturing gradient gel electrophoresis (2D-PAGGE) of normoalphalipoproteinemic plasma and subsequent immunoblotting with anti-apoA-I-antibodies differentiates pre-beta 1-LpA-I, pre-beta 2-LpA-I, pre-beta 3-LpA-I, alpha-LpA-I2, and alpha-LpA-I3. Immunodetection with anti-apoE antibodies differentiates gamma-LpE and alpha-LpE. Pulse-chase incubations of plasma with [3H]unesterified cholesterol ([3H]UC)-labeled fibroblasts and subsequent 2D-PAGGE revealed that cell-derived [3H]UC is taken up by pre-beta 1-LpA-I and gamma-LpE. From these initial acceptors, [3H]UC is transferred to LDL via pre-beta 2-LpA-I-->pre-beta 3-LpA-I-->alpha-LpA-I. Some UC is esterified in pre-beta 3-LpA-I, and some is esterified in alpha-LpA-I after its retransfer from LDL. In this study we investigated the effect of various forms of familial HDL deficiency on reverse cholesterol transport. Plasma samples of patients with various forms of HDL deficiency are characterized by the lack of specific HDL subclasses. ApoE-containing HDLs, including gamma-LpE, are present in all kinds of HDL deficiency. However, all forms of LpA-I are absent in apoA-I-deficient plasma, pre-beta 3-LpA-I and alpha-LpA-I from the plasma of patients with Tangier disease (TD), and pre-beta 3-LpA-I and large alpha-LpA-I from the plasma of patients with lecithin:cholesterol acyltransferase (LCAT) deficiency and fish-eye disease (FED). After a 1-minute pulse with labeled fibroblasts, efflux of [3H]UC into HDL-deficient plasmas decreased, compared with normal plasma, by 49% (apoA-I deficiency), 36% (TD), 21% (LCAT deficiency), and 28% (FED). In apoA-I deficiency, only gamma-LpE takes up cell-derived [3H]UC. In the three other HDL-deficiency states, cell-derived [3H]UC is initially taken up by both pre-beta 1-LpA-I and gamma-LpE. The four HDL deficiencies are also characterized by differences in the esterification of cell-derived [3H]UC. No esterification occurs in LCAT-deficient plasma. In FED plasma, [3H]UC is esterified in LDL. In apoA-I deficiency and TD, however, [3H]UC is esterified in lipoproteins free of apoA-I and apoB. In the two latter cases, the transfer of [3H]cholesteryl ester to LDL is enhanced compared with normal plasma. The lack of specific HDL subclasses and the consequent changes in reverse cholesterol transport pathways differently affect net mass efflux of cholesterol from fibroblasts into HDL-deficient plasma.(ABSTRACT TRUNCATED AT 400 WORDS)

A nonsense mutation in the apolipoprotein A-I gene is associated with high-density lipoprotein deficiency and periorbital xanthelasmas.

Conflicting data from epidemiological trials, genetic family studies, transgenic animal models, and in vitro experiments have created controversy regarding the importance of HDL and apolipoprotein (apo) A-I for reverse cholesterol transport and protection from atherosclerosis. In this study we identified a homozygous nonsense mutation in codon 32 (Q32X) of the apoA-I gene as the molecular basis of apoA-I deficiency in a 31-year-old woman who did not present with clinical signs of atherosclerosis. Despite half-normal plasma concentrations of HDL cholesterol and apoA-I in subjects heterozygous for this mutation, the history of the patient's large family did not indicate any increased prevalence of myocardial infarction.

[Cholesterol embolism: a heavy price to pay after successful fibrinolysis]. / Cholesterinembolien: eine teure Rechnung nach erfolgreicher Fibrinolyse.

We attribute a case of acute irreversible renal failure associated with "blue toe syndrome" and eosinophilia to a cholesterol embolism after "successful" treatment of myocardial infarction with fibrinolysis. This case shows that CE can be caused not only by invasive arterial procedures but also by thrombolytic as well as by anticoagulant treatment. In modern medicine, the importance of this often fatal but usually undetected systemic affection is increasing. For patients with serious atherosclerosis it is essential to analyze the risks and benefits before undertaking arterial invasive procedures or fibrinolysis.

Acute bilateral striatal necrosis in an infant: CT and MRI.

We report a case of acute bilateral striatal necrosis in an infant. CT and MRI findings are described.

[Pravastatin in the treatment of primary hypercholesterolemia: a Swiss multicenter study]. / Pravastatin zur Behandlung der primären Hypercholesterinämie: Schweizer Multizenter-Studie.

Conventional lipid-lowering agents displayed only limited efficacy in lowering total and LDL cholesterol and a high incidence of side effects. Pravastatin is a new potent cholesterol-lowering agent, which selectively inhibits hepatic HMG-CoA-reductase. In a double-blind, placebo-controlled Swiss multicenter study with determination of lipids and lipoprotein in a central laboratory, the efficacy and safety of 6 months' therapy with pravastatin was evaluated in 50 patients with mild hypercholesterolemia and additional coronary risk factors. Compared to baseline and after 26 weeks' therapy, pravastatin significantly reduced total cholesterol (pravastatin vs placebo, -17% vs +7%, p < 0.0001) and LDL cholesterol (-26 vs +2%, p < 0.0001). The total/HDL cholesterol ratio ( = "atherogenic index") was comparable in the two groups at baseline (5.9 +/- 1.1 vs 6.3 +/- 0.9), and was distinctly lowered by pravastatin but not placebo (-20 vs 0%, p < 0.0001). In 11 patients in whom the reduction of serum total cholesterol after 13 weeks' treatment with 20 mg pravastatin was still below target (on average -9.1%), doubling of the dose produced a further decrease of 4.3%. Serum HDL cholesterol and serum triglyceride levels did not change significantly during pravastatin treatment as compared to baseline and placebo. Pravastatin was well tolerated during the 26 weeks without relevant subjective side-effects. There were 5 dropouts during the study, 2 patients in the pravastatin group and 3 in the placebo group. These findings document that pravastatin, administered in a single daily dose of 20 to 40 mg, effectively lowers serum cholesterol and total-/HDL-cholesterol improving action and is well tolerated.